MDedge Dermatology

A one-time dose of two long-acting monoclonal antibodies reduced the risk of developing symptomatic COVID by 77% in comparison with placebo (P < .001) in a randomized, double-blind, placebo-controlled, phase 3 trial in adults, according to researchers who presented results at IDWeek 2021, an annual scientific meeting on infectious diseases.

The mix of tixagevimab and cilgavimab (AZD7442, Astra Zeneca) in a 300-mg dose is delivered in two intramuscular injections.

“This is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention,” said lead author Myron J. Levin, MD, a professor and pediatric infectious disease specialist at the University of Colorado at Denver, Aurora, who presented the findings of the PROVENT trial.

Both antibodies were taken from B cells donated by patients who had been infected with SARS-CoV-2, and they work synergistically, Dr. Levin said.

“The combination of them is better than adding results of each individually,” he said. “In vitro experiments have already shown that variants of interest and concern, including the Delta variant, are successfully neutralized by this cocktail.”

The trial was conducted in 87 sites in the United States, the United Kingdom, Spain, France, and Belgium. Participants included 5,197 unvaccinated adults who had never been infected with SARS-CoV-2 and either were at higher risk for inadequate response to COVID-19 vaccines because they were immunocompromised or were at high risk for exposure.

“Efficacy was observed through at least 3 months,” Dr. Levin said. “Preliminary pharmacokinetic modeling predicts potential protection for up to 12 months.”

Raymund Razonable, MD, an infectious disease expert with the Mayo Clinic in Rochester, Minn., who was not involved with the trial, told this news organization he was particularly interested in this combination because the developers made use of novel technology that extends the half-life of the antibodies and because of the large number of participants in the study.

Modeling that shows protection could last up to a year is novel and important, he said.

“People won’t need frequent injections,” Dr. Razonable said. With postexposure prophylaxis monoclonal cocktails, people may be given a dose a month, he noted.

Dr. Razonable said, “This is something intended to prevent COVID in people who are unvaccinated. The downside to that is we want people to get vaccinated. The best strategy so far is really vaccination.”

He said AZD7442 could potentially help fill the void for patients who are not able to respond to the COVID vaccines, including some who are immunocompromised or are undergoing chemotherapy.

Dr. Razonable said that, although the 77% reduction for developing symptomatic COVID-19 (95% confidence interval vs. placebo, 46.0-90.0; P < .001) is impressive, it is a reduction in relative risk. Still unknown is how much an individual’s absolute risk is reduced.

He also said it would be helpful to know how many people in the study population were immunocompromised, “because I think that’s where this product will be useful for prevention.”

The primary study endpoints were the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to day 183 (efficacy) as well as the safety of the product.

The cocktail appeared to be well tolerated. Adverse events occurred in 35% of participants administered AZD7442 and in 34% of the placebo group. Injection-site reactions occurred in 2.4% of the AZD7442 group and in 2.1% of the placebo group. There was one case of severe or critical COVID-19; two COVID-19–related deaths occurred in the placebo group.

AZD7442 is being developed with the help of funding from the U.S. government. Dr. Levin has received support from GlaxoSmithKline companies. Many of the coauthors are employed by AstraZeneca and hold stock in the company. Dr. Razonable has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A one-time dose of two long-acting monoclonal antibodies reduced the risk of developing symptomatic COVID by 77% in comparison with placebo (P < .001) in a randomized, double-blind, placebo-controlled, phase 3 trial in adults, according to researchers who presented results at IDWeek 2021, an annual scientific meeting on infectious diseases.

The mix of tixagevimab and cilgavimab (AZD7442, Astra Zeneca) in a 300-mg dose is delivered in two intramuscular injections.

“This is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention,” said lead author Myron J. Levin, MD, a professor and pediatric infectious disease specialist at the University of Colorado at Denver, Aurora, who presented the findings of the PROVENT trial.

Both antibodies were taken from B cells donated by patients who had been infected with SARS-CoV-2, and they work synergistically, Dr. Levin said.

“The combination of them is better than adding results of each individually,” he said. “In vitro experiments have already shown that variants of interest and concern, including the Delta variant, are successfully neutralized by this cocktail.”

The trial was conducted in 87 sites in the United States, the United Kingdom, Spain, France, and Belgium. Participants included 5,197 unvaccinated adults who had never been infected with SARS-CoV-2 and either were at higher risk for inadequate response to COVID-19 vaccines because they were immunocompromised or were at high risk for exposure.

“Efficacy was observed through at least 3 months,” Dr. Levin said. “Preliminary pharmacokinetic modeling predicts potential protection for up to 12 months.”

Raymund Razonable, MD, an infectious disease expert with the Mayo Clinic in Rochester, Minn., who was not involved with the trial, told this news organization he was particularly interested in this combination because the developers made use of novel technology that extends the half-life of the antibodies and because of the large number of participants in the study.

Modeling that shows protection could last up to a year is novel and important, he said.

“People won’t need frequent injections,” Dr. Razonable said. With postexposure prophylaxis monoclonal cocktails, people may be given a dose a month, he noted.

Dr. Razonable said, “This is something intended to prevent COVID in people who are unvaccinated. The downside to that is we want people to get vaccinated. The best strategy so far is really vaccination.”

He said AZD7442 could potentially help fill the void for patients who are not able to respond to the COVID vaccines, including some who are immunocompromised or are undergoing chemotherapy.

Dr. Razonable said that, although the 77% reduction for developing symptomatic COVID-19 (95% confidence interval vs. placebo, 46.0-90.0; P < .001) is impressive, it is a reduction in relative risk. Still unknown is how much an individual’s absolute risk is reduced.

He also said it would be helpful to know how many people in the study population were immunocompromised, “because I think that’s where this product will be useful for prevention.”

The primary study endpoints were the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to day 183 (efficacy) as well as the safety of the product.

The cocktail appeared to be well tolerated. Adverse events occurred in 35% of participants administered AZD7442 and in 34% of the placebo group. Injection-site reactions occurred in 2.4% of the AZD7442 group and in 2.1% of the placebo group. There was one case of severe or critical COVID-19; two COVID-19–related deaths occurred in the placebo group.

AZD7442 is being developed with the help of funding from the U.S. government. Dr. Levin has received support from GlaxoSmithKline companies. Many of the coauthors are employed by AstraZeneca and hold stock in the company. Dr. Razonable has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A one-time dose of two long-acting monoclonal antibodies reduced the risk of developing symptomatic COVID by 77% in comparison with placebo (P < .001) in a randomized, double-blind, placebo-controlled, phase 3 trial in adults, according to researchers who presented results at IDWeek 2021, an annual scientific meeting on infectious diseases.

The mix of tixagevimab and cilgavimab (AZD7442, Astra Zeneca) in a 300-mg dose is delivered in two intramuscular injections.

“This is the first long-acting combination of monoclonal antibodies that represents a potential new option to augment COVID-19 prevention,” said lead author Myron J. Levin, MD, a professor and pediatric infectious disease specialist at the University of Colorado at Denver, Aurora, who presented the findings of the PROVENT trial.

Both antibodies were taken from B cells donated by patients who had been infected with SARS-CoV-2, and they work synergistically, Dr. Levin said.

“The combination of them is better than adding results of each individually,” he said. “In vitro experiments have already shown that variants of interest and concern, including the Delta variant, are successfully neutralized by this cocktail.”

The trial was conducted in 87 sites in the United States, the United Kingdom, Spain, France, and Belgium. Participants included 5,197 unvaccinated adults who had never been infected with SARS-CoV-2 and either were at higher risk for inadequate response to COVID-19 vaccines because they were immunocompromised or were at high risk for exposure.

“Efficacy was observed through at least 3 months,” Dr. Levin said. “Preliminary pharmacokinetic modeling predicts potential protection for up to 12 months.”

Raymund Razonable, MD, an infectious disease expert with the Mayo Clinic in Rochester, Minn., who was not involved with the trial, told this news organization he was particularly interested in this combination because the developers made use of novel technology that extends the half-life of the antibodies and because of the large number of participants in the study.

Modeling that shows protection could last up to a year is novel and important, he said.

“People won’t need frequent injections,” Dr. Razonable said. With postexposure prophylaxis monoclonal cocktails, people may be given a dose a month, he noted.

Dr. Razonable said, “This is something intended to prevent COVID in people who are unvaccinated. The downside to that is we want people to get vaccinated. The best strategy so far is really vaccination.”

He said AZD7442 could potentially help fill the void for patients who are not able to respond to the COVID vaccines, including some who are immunocompromised or are undergoing chemotherapy.

Dr. Razonable said that, although the 77% reduction for developing symptomatic COVID-19 (95% confidence interval vs. placebo, 46.0-90.0; P < .001) is impressive, it is a reduction in relative risk. Still unknown is how much an individual’s absolute risk is reduced.

He also said it would be helpful to know how many people in the study population were immunocompromised, “because I think that’s where this product will be useful for prevention.”

The primary study endpoints were the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to day 183 (efficacy) as well as the safety of the product.

The cocktail appeared to be well tolerated. Adverse events occurred in 35% of participants administered AZD7442 and in 34% of the placebo group. Injection-site reactions occurred in 2.4% of the AZD7442 group and in 2.1% of the placebo group. There was one case of severe or critical COVID-19; two COVID-19–related deaths occurred in the placebo group.

AZD7442 is being developed with the help of funding from the U.S. government. Dr. Levin has received support from GlaxoSmithKline companies. Many of the coauthors are employed by AstraZeneca and hold stock in the company. Dr. Razonable has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A phase 3, randomized, double-blind, controlled trial has shown that oteseconazole (Mycovia Pharmaceuticals), an oral antifungal agent, is safe and effective in treating acute and recurrent yeast infections (vulvovaginal candidiasis [VVC]) and in preventing  recurrence of acute VVC episodes.

Findings of the ultraVIOLET trial, which compared oteseconazole with the standard fluconazole, were presented at IDWeek 2021, an annual scientific meeting on infectious diseases, by lead author Mark G. Martens, MD, a professor in the department of obstetrics and gynecology at Drexel University College of Medicine in Philadelphia.

About 75% of all women will have a yeast infection in their lifetime, Dr. Martens noted. About 138 million women worldwide have recurring episodes (at least three acute episodes in the last year) of the debilitating condition.

“Recurrent vulvovaginal candidiasis typically requires treatment of the acute episode followed by long-term suppressive therapy with either weekly or biweekly fluconazole,” Dr. Martens said. However, when therapy stops, more than 50% of patients with recurrent VVC experience an infection within the next 6 months, which takes a significant toll on daily life.

Additionally, fluconazole has been linked with safety issues concerning chronic dosing, he said, citing liver toxicity, drug-drug interactions and “increased risk of miscarriage and birth defects when used during pregnancy.”

Topical treatments have been associated with messy application and burning, he noted.

For this study, researchers enrolled 219 women with a history of recurrent VVC at 51 U.S. sites. Participants were randomized either to 600 mg oteseconazole on day 1, 450 mg oteseconazole on day 2 or placebo capsules; or three sequential 150 mg doses (every 72 hours) of fluconazole together with matching placebo capsules.

In the maintenance phase, 185 women with resolved acute VVC (clinical signs and symptoms were scored below 3) on day 14 received 150 mg oteseconazole or placebo weekly for 11 weeks.

Oteseconazole was superior to fluconazole/placebo in the proportion of subjects with at least one culture-verified acute VVC episode through week 50 in the intent-to-treat population (P < .001) which included subjects who failed to clear their infection in the induction phase.

The average percentage of participants with at least one culture-verified acute VVC episode through week 50 was lower in the oteseconazole group (5.1%), compared with the fluconazole/placebo group (42.2%).

Oteseconazole was noninferior to fluconazole in the proportion of subjects with resolved acute VVC infections at day 14 – 93.2% for the oteseconazole group vs. 95.8% for the fluconazole/placebo group.

The percentages of women who had at least one treatment-emergent adverse event (TEAE) were similar – 54% in the oteseconazole group and 64% in the fluconazole/placebo group.  Most TEAEs were mild or moderate and there were no drug-related SAEs or adverse effects on liver function.

“There was no difference in the two groups in he baseline characteristics of age, race, and history of diabetes,” he said.

Oluwatosin Goje, MD, an ob.gyn. with the Cleveland Clinic told this news organization that the drug may offer another option for women who don’t respond to azoles.

“The CDC guidelines say, and I agree, that most episodes of recurrent VVC that are caused by Candida albicans will respond to topical azoles, to oral azoles, to the known drugs that are available. You just may have to use them for a prolonged period of time,” Dr. Goje said. But some patients won’t respond to azoles, the currently available drugs, and topical treatments – so new options are welcome for them, she noted.

She pointed out that the U.S. Food and Drug Administration in June approved ibrexafungerp (Brexafemme), the first oral nonazole treatment for vaginal yeast infections. It was the first approved medicine in a novel antifungal class in more than 2 decades.

Dr. Goje, who runs a large clinic with substantial numbers of women with recurrent yeast infections, said the psychosocial problems women with recurrent yeast infections face – and the time off work and money spent trying to get temporary relief from over-the-counter medications – is underestimated.

“Women have long suffered vaginitis. It can be a lot of social and economic burden. So anything in the toolbox to help women is welcome,” Dr. Goje said.

The study was sponsored by Mycovia Pharmaceuticals. Dr. Martens reports no relevant financial relationships. Several coauthors are either employees of Mycovia or receive support from the company. Dr. Goje has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Prurigo pigmentosa, an uncommon inflammatory skin condition also known as Nagashima disease, is growing in frequency, possibly as a result of increased interest in the ketogenic diet, according to a dermatologist, who reviewed skin conditions common to patients of Asian descent at the Skin of Color Update 2021.

“Ketogenic diets are gaining popularity globally for weight loss. After 2-4 weeks [on a strict ketogenic diet], some patients start to notice very pruritic papules on their trunk, the so-called keto rash,” reported Hye Jin Chung, MD, director of the Asian Skin Clinic, Beth Israel Deaconess Medical Center, Boston. “Keto rash is actually prurigo pigmentosa.”

The exact pathogenesis of prurigo pigmentosa, a highly pruritic macular and papular rash with gross reticular pigmentation, is unclear, but Dr. Chung reported that the strong link with ketosis might explain why more cases are now being encountered outside of east Asia. Ketosis or conditions associated with a high risk for ketosis, such as anorexia nervosa, diabetes mellitus, or recent bariatric surgery, have been linked to prurigo pigmentosa in all skin types and ethnicities.

“I tell my residents that this is a disease you will never forget after your first case,” she said.

The differential diagnosis includes contact dermatitis and other inflammatory disorders, but Dr. Chung said that the reticular pattern of the lesions is a relatively unique feature. Confluent and reticulated papillomatosis (CARP) shares a pattern of reticulated lesions, but Dr. Chung said it lacks the inflammatory erythematous papules and the severe pruritus common to prurigo pigmentosa.

Histologically, the pattern evolves. It begins as a perivascular infiltration dominated by neutrophils and eosinophils with hyperkeratosis, acanthosis, and spongiosis. Over time, Dr. Chung said that the histologic picture shows an increasing degree of dyskeratosis as keratinocytes die.

Prurigo pigmentosa was first described 50 years ago by Masaji Nagashima, MD, who published a report on eight patients in Japan with a pruriginous truncal dermatosis featuring symmetrical pigmentation. Most subsequent reports were also from Japan or other east Asian countries, but it has since spread.

This global spread was captured in a recently published review of 115 published studies and case reports from 24 countries. In this review, the proportion of studies from Europe (36.5%) approached that of those from east Asia (38.2%), even if 76% of the patients for whom race was reported were of Asian ethnicity.

Of the 369 patients evaluated in these studies and case reports, 72.1% were female. The mean age was 25.6 years. In the studies originating outside of Asia, prurigo pigmentosa was reported in a spectrum of skin types and ethnicities, including Whites, Blacks, and Hispanics. The lowest reported incidence has been in the latter two groups, but the authors of the review speculated that this condition is likely being underdiagnosed in non-Asian individuals.

Dr. Chung agreed, and she cautioned that the consequences typically result in a significant delay for achieving disease control. In recounting a recent case of prurigo pigmentosa at her center, she said that the 59-year-old Asian patient had been initiated on topical steroids and oral antihistamines by her primary care physician before she was referred. This is a common and reasonable strategy for a highly pruritic rash potentially caused by contact dermatitis, but it is ineffective for this disorder.

“Prurigo pigmentosa requires anti-inflammatory agents,” she explained. She said that doxycycline and minocycline are the treatments of choice, but noted that there are also reports of efficacy with dapsone, macrolide antibiotics, and isotretinoin.

In her most recent case, she initiated the patient on 100 mg of doxycycline twice daily. There was significant improvement within 2 weeks, and the rash resolved within a month with no relapse in follow-up that now exceeds 12 months, Dr. Chung said.

According to Dr. Chung, Asian-Americans are the most rapidly growing ethnic group in the United States, making it increasingly important to be familiar with conditions common or unique to Asian skin, but prurigo pigmentosa is no longer confined to those of Asian descent. She encouraged clinicians to recognize this disorder to reduce the common delays to effective treatment.

The senior author of the recently published review of studies, Jensen Yeung, MD, of the department of dermatology, University of Toronto, agreed. He, too, believes that dermatologists need to increase their awareness of the signs and symptoms of prurigo pigmentosa – and not just in Asian patients or patients of Asian descent.

“This diagnosis is often missed,” he contended in an interview. “This condition has become more common in the past 5 years in my clinical experience.” He added that the increasing incidence might not just be related to better diagnostic accuracy, although the most significant of other possible explanations “is not yet well understood.”

Dr. Chung reports that she has no relevant financial relationships to disclose. Dr. Yeung reports financial relationships with more than 25 pharmaceutical companies, some of which produce treatments employed in the control of prurigo pigmentosa.

Prurigo pigmentosa, an uncommon inflammatory skin condition also known as Nagashima disease, is growing in frequency, possibly as a result of increased interest in the ketogenic diet, according to a dermatologist, who reviewed skin conditions common to patients of Asian descent at the Skin of Color Update 2021.

“Ketogenic diets are gaining popularity globally for weight loss. After 2-4 weeks [on a strict ketogenic diet], some patients start to notice very pruritic papules on their trunk, the so-called keto rash,” reported Hye Jin Chung, MD, director of the Asian Skin Clinic, Beth Israel Deaconess Medical Center, Boston. “Keto rash is actually prurigo pigmentosa.”

The exact pathogenesis of prurigo pigmentosa, a highly pruritic macular and papular rash with gross reticular pigmentation, is unclear, but Dr. Chung reported that the strong link with ketosis might explain why more cases are now being encountered outside of east Asia. Ketosis or conditions associated with a high risk for ketosis, such as anorexia nervosa, diabetes mellitus, or recent bariatric surgery, have been linked to prurigo pigmentosa in all skin types and ethnicities.

“I tell my residents that this is a disease you will never forget after your first case,” she said.

The differential diagnosis includes contact dermatitis and other inflammatory disorders, but Dr. Chung said that the reticular pattern of the lesions is a relatively unique feature. Confluent and reticulated papillomatosis (CARP) shares a pattern of reticulated lesions, but Dr. Chung said it lacks the inflammatory erythematous papules and the severe pruritus common to prurigo pigmentosa.

Histologically, the pattern evolves. It begins as a perivascular infiltration dominated by neutrophils and eosinophils with hyperkeratosis, acanthosis, and spongiosis. Over time, Dr. Chung said that the histologic picture shows an increasing degree of dyskeratosis as keratinocytes die.

Prurigo pigmentosa was first described 50 years ago by Masaji Nagashima, MD, who published a report on eight patients in Japan with a pruriginous truncal dermatosis featuring symmetrical pigmentation. Most subsequent reports were also from Japan or other east Asian countries, but it has since spread.

This global spread was captured in a recently published review of 115 published studies and case reports from 24 countries. In this review, the proportion of studies from Europe (36.5%) approached that of those from east Asia (38.2%), even if 76% of the patients for whom race was reported were of Asian ethnicity.

Of the 369 patients evaluated in these studies and case reports, 72.1% were female. The mean age was 25.6 years. In the studies originating outside of Asia, prurigo pigmentosa was reported in a spectrum of skin types and ethnicities, including Whites, Blacks, and Hispanics. The lowest reported incidence has been in the latter two groups, but the authors of the review speculated that this condition is likely being underdiagnosed in non-Asian individuals.

Dr. Chung agreed, and she cautioned that the consequences typically result in a significant delay for achieving disease control. In recounting a recent case of prurigo pigmentosa at her center, she said that the 59-year-old Asian patient had been initiated on topical steroids and oral antihistamines by her primary care physician before she was referred. This is a common and reasonable strategy for a highly pruritic rash potentially caused by contact dermatitis, but it is ineffective for this disorder.

“Prurigo pigmentosa requires anti-inflammatory agents,” she explained. She said that doxycycline and minocycline are the treatments of choice, but noted that there are also reports of efficacy with dapsone, macrolide antibiotics, and isotretinoin.

In her most recent case, she initiated the patient on 100 mg of doxycycline twice daily. There was significant improvement within 2 weeks, and the rash resolved within a month with no relapse in follow-up that now exceeds 12 months, Dr. Chung said.

According to Dr. Chung, Asian-Americans are the most rapidly growing ethnic group in the United States, making it increasingly important to be familiar with conditions common or unique to Asian skin, but prurigo pigmentosa is no longer confined to those of Asian descent. She encouraged clinicians to recognize this disorder to reduce the common delays to effective treatment.

The senior author of the recently published review of studies, Jensen Yeung, MD, of the department of dermatology, University of Toronto, agreed. He, too, believes that dermatologists need to increase their awareness of the signs and symptoms of prurigo pigmentosa – and not just in Asian patients or patients of Asian descent.

“This diagnosis is often missed,” he contended in an interview. “This condition has become more common in the past 5 years in my clinical experience.” He added that the increasing incidence might not just be related to better diagnostic accuracy, although the most significant of other possible explanations “is not yet well understood.”

Dr. Chung reports that she has no relevant financial relationships to disclose. Dr. Yeung reports financial relationships with more than 25 pharmaceutical companies, some of which produce treatments employed in the control of prurigo pigmentosa.

Prurigo pigmentosa, an uncommon inflammatory skin condition also known as Nagashima disease, is growing in frequency, possibly as a result of increased interest in the ketogenic diet, according to a dermatologist, who reviewed skin conditions common to patients of Asian descent at the Skin of Color Update 2021.

“Ketogenic diets are gaining popularity globally for weight loss. After 2-4 weeks [on a strict ketogenic diet], some patients start to notice very pruritic papules on their trunk, the so-called keto rash,” reported Hye Jin Chung, MD, director of the Asian Skin Clinic, Beth Israel Deaconess Medical Center, Boston. “Keto rash is actually prurigo pigmentosa.”

The exact pathogenesis of prurigo pigmentosa, a highly pruritic macular and papular rash with gross reticular pigmentation, is unclear, but Dr. Chung reported that the strong link with ketosis might explain why more cases are now being encountered outside of east Asia. Ketosis or conditions associated with a high risk for ketosis, such as anorexia nervosa, diabetes mellitus, or recent bariatric surgery, have been linked to prurigo pigmentosa in all skin types and ethnicities.

“I tell my residents that this is a disease you will never forget after your first case,” she said.

The differential diagnosis includes contact dermatitis and other inflammatory disorders, but Dr. Chung said that the reticular pattern of the lesions is a relatively unique feature. Confluent and reticulated papillomatosis (CARP) shares a pattern of reticulated lesions, but Dr. Chung said it lacks the inflammatory erythematous papules and the severe pruritus common to prurigo pigmentosa.

Histologically, the pattern evolves. It begins as a perivascular infiltration dominated by neutrophils and eosinophils with hyperkeratosis, acanthosis, and spongiosis. Over time, Dr. Chung said that the histologic picture shows an increasing degree of dyskeratosis as keratinocytes die.

Prurigo pigmentosa was first described 50 years ago by Masaji Nagashima, MD, who published a report on eight patients in Japan with a pruriginous truncal dermatosis featuring symmetrical pigmentation. Most subsequent reports were also from Japan or other east Asian countries, but it has since spread.

This global spread was captured in a recently published review of 115 published studies and case reports from 24 countries. In this review, the proportion of studies from Europe (36.5%) approached that of those from east Asia (38.2%), even if 76% of the patients for whom race was reported were of Asian ethnicity.

Of the 369 patients evaluated in these studies and case reports, 72.1% were female. The mean age was 25.6 years. In the studies originating outside of Asia, prurigo pigmentosa was reported in a spectrum of skin types and ethnicities, including Whites, Blacks, and Hispanics. The lowest reported incidence has been in the latter two groups, but the authors of the review speculated that this condition is likely being underdiagnosed in non-Asian individuals.

Dr. Chung agreed, and she cautioned that the consequences typically result in a significant delay for achieving disease control. In recounting a recent case of prurigo pigmentosa at her center, she said that the 59-year-old Asian patient had been initiated on topical steroids and oral antihistamines by her primary care physician before she was referred. This is a common and reasonable strategy for a highly pruritic rash potentially caused by contact dermatitis, but it is ineffective for this disorder.

“Prurigo pigmentosa requires anti-inflammatory agents,” she explained. She said that doxycycline and minocycline are the treatments of choice, but noted that there are also reports of efficacy with dapsone, macrolide antibiotics, and isotretinoin.

In her most recent case, she initiated the patient on 100 mg of doxycycline twice daily. There was significant improvement within 2 weeks, and the rash resolved within a month with no relapse in follow-up that now exceeds 12 months, Dr. Chung said.

According to Dr. Chung, Asian-Americans are the most rapidly growing ethnic group in the United States, making it increasingly important to be familiar with conditions common or unique to Asian skin, but prurigo pigmentosa is no longer confined to those of Asian descent. She encouraged clinicians to recognize this disorder to reduce the common delays to effective treatment.

The senior author of the recently published review of studies, Jensen Yeung, MD, of the department of dermatology, University of Toronto, agreed. He, too, believes that dermatologists need to increase their awareness of the signs and symptoms of prurigo pigmentosa – and not just in Asian patients or patients of Asian descent.

“This diagnosis is often missed,” he contended in an interview. “This condition has become more common in the past 5 years in my clinical experience.” He added that the increasing incidence might not just be related to better diagnostic accuracy, although the most significant of other possible explanations “is not yet well understood.”

Dr. Chung reports that she has no relevant financial relationships to disclose. Dr. Yeung reports financial relationships with more than 25 pharmaceutical companies, some of which produce treatments employed in the control of prurigo pigmentosa.

Racial and ethnic disparities persist in the use of Mohs surgery to treat dermatofibrosarcoma protuberans, according to the results of a retrospective cohort study of more than 2,000 patients.

Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.

In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.

Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”

In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.

The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.

“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Racial and ethnic disparities persist in the use of Mohs surgery to treat dermatofibrosarcoma protuberans, according to the results of a retrospective cohort study of more than 2,000 patients.

Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.

In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.

Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”

In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.

The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.

“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Racial and ethnic disparities persist in the use of Mohs surgery to treat dermatofibrosarcoma protuberans, according to the results of a retrospective cohort study of more than 2,000 patients.

Current guidelines recommend Mohs micrographic surgery (MMS) as a first-line treatment for dermatofibrosarcoma protuberans, but the procedure may be inaccessible for certain populations and in some geographic areas, wrote Kevin J. Moore, MD, and Michael S. Chang, BA, of the department of dermatology, Brigham and Women’s Hospital, Boston, and colleagues. Wide local excision (WLE) is a less effective option; recurrence rates associated with this treatment are approximately 30% because of incomplete margin assessment, compared with about 3% with MMS, they noted.

In the study, published as a letter in the Journal of the American Academy of Dermatology, the investigators identified 2,370 cases of dermatofibrosarcoma protuberans using data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Registry from 2000 to 2018. The mean age of the patients was 44 years; 55% were women. A total of 539 patients underwent MMS and 1,831 underwent WLE.

Overall, patients in the WLE group were more likely to be younger, male, Black, and single, the researchers noted. Those who had WLE, they added, were “more commonly deceased at study end date, recipients of adjuvant chemotherapy or radiation, and had truncal tumor locations.”

In a multivariate analysis, patients who were non-Hispanic, White, or other races (including American Indian, Alaskan Native, and Pacific Islander), were significantly more likely to undergo MMS compared with Black and Hispanic patients (adjusted odd ratio [aOR], 1.46, 1.66, and 2.42, respectively). Women were also significantly more likely than were men to undergo MMS (aOR, 1.24). Individuals living in the Western part of the United States were significantly more likely to undergo MMS.

The study findings were limited by several factors including the inability to control for insurance status, lack of data on re-excision, and the use of aggregate case data, the researchers noted. However, the results highlight the disparities in use of MMS for dermatofibrosarcoma protuberans, they said.

“Because MMS is associated with significantly improved outcomes, identifying at-risk patient populations and barriers to accessing MMS is essential,” the researchers noted. The results suggest that disparities persist in accessing MMS for many patients, notably Black and Hispanic males, they said. “Further work is necessary to identify mechanisms for increasing access to MMS,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

The proportion of patients who obtained an opioid prescription for hydrocodone after Mohs micrographic surgery fell by 21.7% between 2011 and 2020, while the use of tramadol increased by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.

The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.

“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”

As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.

“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”

The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.

The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.

“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.

“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”

State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.

“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”

Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”

Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.

“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”

The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.

[email protected]

The proportion of patients who obtained an opioid prescription for hydrocodone after Mohs micrographic surgery fell by 21.7% between 2011 and 2020, while the use of tramadol increased by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.

The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.

“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”

As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.

“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”

The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.

The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.

“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.

“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”

State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.

“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”

Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”

Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.

“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”

The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.

[email protected]

The proportion of patients who obtained an opioid prescription for hydrocodone after Mohs micrographic surgery fell by 21.7% between 2011 and 2020, while the use of tramadol increased by 26.3% between 2009 and 2020, according to a cross-sectional analysis of national insurance claims data.

The findings suggest that dermatologic surgeons generally understood opioid prescription risks and public health warnings about the opioid epidemic, corresponding study author Surya A. Veerabagu said in an interview.

“The frequency of opioid prescriptions after Mohs surgery went up a little bit from 2009 to 2011, but then it subsequently decreased,” said Ms. Veerabagu, a 4th-year student at Tulane University, New Orleans. “It very much correlates with the overarching opioid trends of the time. From 2010 to 2015, research questioning the safety of opioids increased and in 2012, national prescriptions claims for opioids began to decrease. More media outlets voiced concerns over the growing opioid epidemic, as well.”

As she and her associates noted in their study, published online Sept. 22 in JAMA Dermatology, sales of opioids skyrocketed, increasing by 400% from 1999 to 2011, while prescription opioid–related deaths exceeded deaths caused by heroin and cocaine combined.

“In 2016, the U.S. Department of Health and Human Services declared the opioid epidemic a public health emergency, and the Centers for Disease Control and Prevention released guidelines to curtail unnecessary opioid prescriptions,” they wrote. “Unfortunately, overdose deaths involving prescription opioids continued to increase even after these measures.”

The researchers drew from Optum Clinformatics Data Mart (Optum CDM), a nationally representative insurance claims database, and limited the analysis to 358,012 adults who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery in the United States from Jan. 1, 2009, to June 1, 2020. They found that 34.6% of patients underwent Mohs surgery with opioid claims in 2009. This rose to a peak of 39.6% in 2011, then decreased annually to a rate of 11.7% in 2020.

The four opioids obtained most during the study period were hydrocodone (55%), codeine (16.3%), oxycodone (12%), and tramadol (11.6%). However, over time, the proportion of patients who obtained hydrocodone fell 21.7% from a peak of 67.1% in 2011 to 45.4% in 2020, while the proportion of patients who obtained tramadol – generally recognized as a safer option – increased 26.3% from a low of 1.6% in 2009 to 27.9% in 2020.

“The switch from very addictive opioids like hydrocodone and oxycodone to weaker opioids like tramadol was fascinating to see,” said Ms. Veerabagu, who conducted the study during her research fellowship in the department of dermatology at the University of Pennsylvania, Philadelphia. “I remember at first thinking I had coded the data wrong. I reviewed the results with the team to ensure it was correct. We noticed that propoxyphene prescriptions suddenly dropped to 0% in 2011.” She found that the FDA warning in 2010 and recall regarding the use of propoxyphene because of cardiotoxicity correlated with her data, which, “in addition to the thorough review, convinced me that my coding was correct.” Prior to 2011, propoxyphene constituted 28% of prescriptions in 2009 and 24% of prescriptions in 2010.

In an interview, Maryam M. Asgari, MD, professor of dermatology at Harvard Medical School, Boston, said that the findings support recent opioid prescription recommendations following Mohs and other dermatologic procedures from professional societies including those from the American College of Mohs Surgery.

“More awareness has been raised in the past decade regarding the opioid epidemic and the rise of opioid abuse and deaths,” she said. “There has been increased scrutiny on procedures and prescribing of opioids post procedures.”

State-led efforts to lower the number of opioid prescriptions also play a role. For example, in 2016, Massachusetts launched the Massachusetts Prescription Awareness Tool (MassPAT), which imposes a 7-day limit on first-time prescriptions of opioids to patients and mandates that all prescribers check the prescription drug monitoring program before prescribing schedule II or III substances.

“The MassPAT system also gives you quarterly data on how your opioid prescriptions compare with those of your peers within your specialty and subspecialty,” Dr. Asgari said. “If you’re an outlier, I think that quickly leads you to change your prescribing patterns.”

Dr. Asgari noted that most opioids prescribed in the study by Ms. Veerabagu and colleagues were for cancers that arose on the head and neck. “There is still a perception among providers that cancers that arise in those anatomic sites can potentially cause more discomfort for the patient,” she said. “So, knowing more about the degree of pain among the head and neck cases would be an area of knowledge that would help provider behavior down the line.”

Ms. Veerabagu acknowledged certain limitations of the study, including the fact that unfilled prescriptions could not be accounted for, nor could opioids not taken or those obtained without a prescription. “We cannot survey patients in insurance claims database studies, so we have no way of knowing if everyone’s pain was adequately controlled from 2009 to 2020,” she said.

“The main takeaway message is to make sure doctors and patients share an open dialogue,” she added. “Informing patients of the major pros and cons of the appropriate postoperative pain management options available, including opioids’ addiction potential, is crucial. We hope our study adds to the larger continuing conversation of opioid usage within dermatology.”

The study’s senior author was Cerrene N. Giordano, MD, of the department of dermatology at the Hospital of the University of Pennsylvania, Philadelphia. Coauthor Jeremy R. Etzkorn, MD, is supported by a Dermatology Foundation Career Development Award in Dermatologic Surgery; coauthor Megan H. Noe, MD, MPH, reported receiving grants from Boehringer Ingelheim outside the submitted work. Another coauthor, Thuzar M. Shin, MD, PhD, reported receiving grants from Regeneron outside the submitted work. Dr. Asgari disclosed that she has received support from the Melanoma Research Alliance. She also contributes a chapter on skin cancer to UpToDate, for which she receives royalties.

[email protected]

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

Topical and oral Janus Kinase (JAK)-inhibitors are important new additions to the therapeutic armamentarium of atopic dermatitis (AD). I recently addressed some important treatment considerations regarding the JAK-inhibitors. In just two short months, there have already been a number of important new publications on JAK-inhibitors in AD that provide crucial data to guide treatment decisions.

Topical ruxolitinib 1.5% cream (a JAK1/2 inhibitor) was just approved by United States Food and Drug Administration for the treatment of mild-moderate AD. Clinicians always want to know about the comparative effectiveness of new agents compared to already approved agents. A previous phase 2B randomized controlled trial (RCT) compared multiple doses of ruxolitinib cream with a vehicle control and triamcinolone 0.1% cream active comparator¹. Topical ruxolitinib 1.5% cream was significantly more effective than vehicle and numerically more effective than triamcinolone 0.1% cream.

Zhang et al. recently conducted a network meta-analysis of 10 RCT for topical JAK and phosphodiesterase E4 (PDE4)-inhibitors, mostly with mild-to-moderate AD. All included JAK inhibitors showed higher Investigators Global Assessment (IGA) response vs. vehicle, with ruxolitinib 1.5% once daily showing similar efficacy as tofacitinib 2% and delgocitinib 3% twice daily. Whereas, topical tacrolimus 0.1% and hydrocortisone butyrate 0.1% twice a day were not more effective than vehicle at achieving IGA response. These results suggest that topical ruxolitinib and other JAK-inhibitors are more effective at clearing AD lesions than currently used topical therapies.

There has been a recent flurry of publications regarding the efficacy and safety of abrocitinib (an oral, once daily, JAK1 inhibitor) in moderate-severe atopic dermatitis.

• Eichenfield et al. published the results of the JADE TEEN study ², a phase 3 RCT of abrocitinib in adolescents. Abrocitinib 200 mg and 100 mg resulted in significant improvements of IGA, Eczema Area and Severity Index, and itch scores, etc. over a 12-week treatment period compared to placebo. These results support the efficacy of abrocitinib in adolescents with moderate-severe AD.
• Simpson et al. published the results from an integrated safety analysis of pooled data from 5 short-term and 1 long-term extension study of abrocitinib therapy ³. Abrocitinib 200 mg and 100 mg doses were well-tolerated during 12-week placebo controlled trials, with nausea, headache, and acne being the most common adverse-events. The incidence of different adverse-events did not consistently increase over time. However, there were some rare events reported for venous thromboembolism and deaths. These results indicate an overall good safety profile for abrocitinib, but proper patient and dose selection should be carefully considered.
• Additionally, strategies should be employed to potentially minimize risk of adverse-events. One such approach is flexible dosing in order to maintain long-term disease control using the lowest amount of medicine needed. Blauvelt et al. published findings from the JADE REGIMEN study ⁴. Patients who responded to 12 weeks of abrocitinib 200 mg open-label monotherapy were randomly assigned to abrocitinib 200 mg, abrocitinib 100 mg, or placebo maintenance therapy for 40-weeks. Flares occurred least commonly in patients maintained on abrocitinib 200 mg (18.9%), followed by abrocitinib 100 mg (42.6%), and most commonly for placebo (80.9%). These results indicate that a large subset of patients who achieve clinical response with abrocitinib 200 mg could be maintained on a lower dose of 100 mg and in some cases may even be able to have a drug holiday without flaring. While similar studies were not performed for other oral JAK-inhibitors, it may be that lower maintenance dosing may also be feasible and effective for other oral JAK-inhibitors. Future research is needed to identify patient subsets who will most likely maintain clinical response with lower maintenance dosing of oral JAK-inhibitors.

1. Kim BS, Howell MD, Sun K, et al. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. The Journal of allergy and clinical immunology. 2020;145(2):572-582.
2. Eichenfield LF, Flohr C, Sidbury R, et al. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial. JAMA dermatology. 2021.
3. Simpson EL, Silverberg JI, Nosbaum A, et al. Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program. American journal of clinical dermatology. 2021;22(5):693-707.
4. Blauvelt A, Silverberg JI, Lynde CW, et al. Abrocitinib induction, randomized withdrawal, and retreatment in patients with moderate-to-severe atopic dermatitis: Results from the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) REGIMEN phase 3 trial. Journal of the American Academy of Dermatology.

High-potency topical steroids such as clobetasol are commonly used as first-line treatment for psoriasis. A recent study (Sidgiddi S et al. Dermatol Ther (Heidelb). 2021 Aug 28) compared the efficacy and safety of clobetasol 0.05% vs. 0.025% cream.  Patients were randomized to receive either clobetasol 0.05% cream or one of two different formulations of clobetasol 0.025% cream twice a day for two weeks. PGA success rates (clear or almost clear skin) were higher with the 0.025% formulations (38.9% and 36.8%) than with the 0.05% cream (30.8%). Safety also appeared to be better or comparable with the 0.025% formulation as measured by the proportion of patients with an abnormal ACTH stimulation test (20.7% and 17.2% in the 0.025% group compared with 30.0% in the 0.05% group). Due to the small study size (88 subjects) these differences did not reach statistical significance, although they suggest that high efficacy and perhaps better safety (reduced hypothalamic–pituitary–adrenal axis suppression) can be achieved with lower concentration formulations of clobetasol cream.

The oral phosphodiesterase 4 inhibitor apremilast is FDA-approved to treat psoriasis and psoriatic arthritis and recent studies have shown that it is more effective than placebo in treating patients with mild-moderate psoriasis and scalp psoriasis. A recent prospective cohort study followed 45 adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more treated with apremilast 30 mg twice daily for 52 weeks (Muñoz-Santos C et al. J Dermatol. 2021 Aug 12). The primary endpoint, the percentage of patients with a Nail Assessment in Psoriasis and Psoriatic Arthritis-Patient Benefit Index of 2 or more at week 52, was achieved in 52% of patients. A median improvement of 53% in fingernail NAPSI score and a mean reduction in nail pain of 68% were observed at week 52.  These findings show that apremilast can be useful in improving the quality-of-life impairment caused by nail psoriasis.

Traditional systemic therapies such as methotrexate and acitretin are cost-effective options for many psoriasis patients. The association of psoriasis with other comorbid conditions, particularly cardiovascular disease, has raised awareness of the importance of considering how therapies impact not just skin disease but also the risk posed by these psoriasis-associated comorbidities. A large Taiwanese retrospective cohort study compared patients treated with methotrexate (13,777) or acitretin (6,020) and found that in comparison to those treated with acitretin, patients treated with methotrexate were at lower risk of experiencing adverse cardiovascular outcomes, including ischemic heart disease and stroke, (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.76-0.94) and had a lower risk of all-cause mortality (aHR, 0.75; 95% CI, 0.66-0.85).

Many disease and patient factors must be considered when choosing the right therapy for a patient. These studies provide valuable information to incorporate into this process and highlight the utility of topical and oral therapies for psoriasis.

High-potency topical steroids such as clobetasol are commonly used as first-line treatment for psoriasis. A recent study (Sidgiddi S et al. Dermatol Ther (Heidelb). 2021 Aug 28) compared the efficacy and safety of clobetasol 0.05% vs. 0.025% cream.  Patients were randomized to receive either clobetasol 0.05% cream or one of two different formulations of clobetasol 0.025% cream twice a day for two weeks. PGA success rates (clear or almost clear skin) were higher with the 0.025% formulations (38.9% and 36.8%) than with the 0.05% cream (30.8%). Safety also appeared to be better or comparable with the 0.025% formulation as measured by the proportion of patients with an abnormal ACTH stimulation test (20.7% and 17.2% in the 0.025% group compared with 30.0% in the 0.05% group). Due to the small study size (88 subjects) these differences did not reach statistical significance, although they suggest that high efficacy and perhaps better safety (reduced hypothalamic–pituitary–adrenal axis suppression) can be achieved with lower concentration formulations of clobetasol cream.

The oral phosphodiesterase 4 inhibitor apremilast is FDA-approved to treat psoriasis and psoriatic arthritis and recent studies have shown that it is more effective than placebo in treating patients with mild-moderate psoriasis and scalp psoriasis. A recent prospective cohort study followed 45 adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more treated with apremilast 30 mg twice daily for 52 weeks (Muñoz-Santos C et al. J Dermatol. 2021 Aug 12). The primary endpoint, the percentage of patients with a Nail Assessment in Psoriasis and Psoriatic Arthritis-Patient Benefit Index of 2 or more at week 52, was achieved in 52% of patients. A median improvement of 53% in fingernail NAPSI score and a mean reduction in nail pain of 68% were observed at week 52.  These findings show that apremilast can be useful in improving the quality-of-life impairment caused by nail psoriasis.

Traditional systemic therapies such as methotrexate and acitretin are cost-effective options for many psoriasis patients. The association of psoriasis with other comorbid conditions, particularly cardiovascular disease, has raised awareness of the importance of considering how therapies impact not just skin disease but also the risk posed by these psoriasis-associated comorbidities. A large Taiwanese retrospective cohort study compared patients treated with methotrexate (13,777) or acitretin (6,020) and found that in comparison to those treated with acitretin, patients treated with methotrexate were at lower risk of experiencing adverse cardiovascular outcomes, including ischemic heart disease and stroke, (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.76-0.94) and had a lower risk of all-cause mortality (aHR, 0.75; 95% CI, 0.66-0.85).

Many disease and patient factors must be considered when choosing the right therapy for a patient. These studies provide valuable information to incorporate into this process and highlight the utility of topical and oral therapies for psoriasis.

High-potency topical steroids such as clobetasol are commonly used as first-line treatment for psoriasis. A recent study (Sidgiddi S et al. Dermatol Ther (Heidelb). 2021 Aug 28) compared the efficacy and safety of clobetasol 0.05% vs. 0.025% cream.  Patients were randomized to receive either clobetasol 0.05% cream or one of two different formulations of clobetasol 0.025% cream twice a day for two weeks. PGA success rates (clear or almost clear skin) were higher with the 0.025% formulations (38.9% and 36.8%) than with the 0.05% cream (30.8%). Safety also appeared to be better or comparable with the 0.025% formulation as measured by the proportion of patients with an abnormal ACTH stimulation test (20.7% and 17.2% in the 0.025% group compared with 30.0% in the 0.05% group). Due to the small study size (88 subjects) these differences did not reach statistical significance, although they suggest that high efficacy and perhaps better safety (reduced hypothalamic–pituitary–adrenal axis suppression) can be achieved with lower concentration formulations of clobetasol cream.

The oral phosphodiesterase 4 inhibitor apremilast is FDA-approved to treat psoriasis and psoriatic arthritis and recent studies have shown that it is more effective than placebo in treating patients with mild-moderate psoriasis and scalp psoriasis. A recent prospective cohort study followed 45 adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more treated with apremilast 30 mg twice daily for 52 weeks (Muñoz-Santos C et al. J Dermatol. 2021 Aug 12). The primary endpoint, the percentage of patients with a Nail Assessment in Psoriasis and Psoriatic Arthritis-Patient Benefit Index of 2 or more at week 52, was achieved in 52% of patients. A median improvement of 53% in fingernail NAPSI score and a mean reduction in nail pain of 68% were observed at week 52.  These findings show that apremilast can be useful in improving the quality-of-life impairment caused by nail psoriasis.

Traditional systemic therapies such as methotrexate and acitretin are cost-effective options for many psoriasis patients. The association of psoriasis with other comorbid conditions, particularly cardiovascular disease, has raised awareness of the importance of considering how therapies impact not just skin disease but also the risk posed by these psoriasis-associated comorbidities. A large Taiwanese retrospective cohort study compared patients treated with methotrexate (13,777) or acitretin (6,020) and found that in comparison to those treated with acitretin, patients treated with methotrexate were at lower risk of experiencing adverse cardiovascular outcomes, including ischemic heart disease and stroke, (adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.76-0.94) and had a lower risk of all-cause mortality (aHR, 0.75; 95% CI, 0.66-0.85).

Many disease and patient factors must be considered when choosing the right therapy for a patient. These studies provide valuable information to incorporate into this process and highlight the utility of topical and oral therapies for psoriasis.

Deucravacitinib, a novel inhibitor of tyrosine kinase 2 (TYK2), continues to demonstrate strong efficacy and acceptable safety after 52 weeks of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).

“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.

The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.

For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).

By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.

By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.

The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.

When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.

On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.

Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.

“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.

In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.

Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.

In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.

The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.

“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.

Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.

“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.

“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.

The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Deucravacitinib, a novel inhibitor of tyrosine kinase 2 (TYK2), continues to demonstrate strong efficacy and acceptable safety after 52 weeks of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).

“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.

The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.

For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).

By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.

By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.

The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.

When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.

On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.

Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.

“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.

In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.

Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.

In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.

The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.

“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.

Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.

“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.

“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.

The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Deucravacitinib, a novel inhibitor of tyrosine kinase 2 (TYK2), continues to demonstrate strong efficacy and acceptable safety after 52 weeks of follow-up, according to late-breaking data from two pivotal trials presented at the virtual annual congress of the European Academy of Dermatology and Venereology.

From benefit reported on the two coprimary endpoints previously reported at 16 weeks, longer follow-up showed further gains out to 24 weeks and then persistent efficacy out to 52 weeks across these and multiple secondary endpoints, reported Richard Warren, MBChB, PhD, professor of dermatology and therapeutics, University of Manchester (England).

“This could be a unique oral therapy and an important treatment option for moderate to severe psoriasis,” Dr. Warren contended.

The multinational double-blind trials, called POETYK PSO-1 and PSO-2, enrolled 666 and 1,020 patients, respectively. The designs were similar. Patients with moderate to severe plaque psoriasis were randomly assigned in a 2:1:1 ratio to deucravacitinib (6 mg once daily), placebo, or apremilast (Otezla; 30 mg twice daily). At 16 weeks, those on placebo were switched to deucravacitinib.

For the coprimary endpoint of PASI 75 (75% clearance on the Psoriasis and Severity Index), the similar rate of response for deucravacitinib in the two studies (58.7%/53.6%) at week 16 was superior to the rates observed on both apremilast (35.1%/40.2%) and placebo (12.7%/9.4%).

By week 24, the proportion of deucravacitinib patients with a PASI 75 response had reached 69.3% and 58.7% in the POETYK PSO-1 and PSO-2 trials, respectively. The proportion of patients on apremilast with PASI 75 at this time point did not increase appreciably in one study and fell modestly in the other.

By week 52, the response rates achieved with deucravacitinib at week 24 were generally unchanged and nearly double those observed on apremilast.

The pattern of relative benefit on the other coprimary endpoint, which was a score of 0 or 1, signifying clear or almost clear skin on the static Physicians Global Assessment (sPGA), followed the same pattern. At week 16, 53.6% of patients had achieved sPGA 0/1. This was significantly higher than that observed on either apremilast or placebo, and this level of response was sustained through week 52.

When patients on placebo were switched to deucravacitinib at week 16, the PASI 75 response climbed quickly. There was complete catch-up by 32 weeks. In both groups, a PASI 75 response rate of about 65% or higher was maintained for the remainder of the study.

On a prespecified analysis, prior treatment exposure was not associated with any impact on the degree of response with deucravacitinib. This included a comparison between patients exposed to no prior biologic, one prior biologic, or two or more biologics, Dr. Warren reported.

Unlike patients in POETYK PSO-1, those with a PASI 75 response at 16 weeks in the POETYK PSO-2 trial were rerandomized to remain on deucravacitinib or switch to placebo. Designed to evaluate response durability, this analysis showed a relatively gradual decline in disease control.

“The median time to a loss of response was 12 weeks,” Dr. Warren said. He was referring in this case to the PASI 75 response, but the slope of decline was similar for sPGA score 0/1. At the end of 52 weeks, 31.3% of patients who had been rerandomized to placebo still maintained a PASI 75 while 80.4% of those who stayed on deucravacitinib still had PASI 75 clearance.

In the 52-week data from these two trials, several secondary endpoints have already been examined, and Dr. Warren said more analyses are coming. So far, the pattern of response has been similar for all endpoints.

Reporting on one as an example, Dr. Warren said that sPGA 0/1 for scalp psoriasis was achieved at week 16 by 70.3% of those randomly assigned to deucravacitinib versus 17.4% of those in the placebo arm. Among those switched from placebo to deucravacitinib at 16 weeks, the scalp response had caught up to that observed in those initiated on deucravacitinib by week 28. The response was sustained out to 52 weeks in both groups.

In the long-term trials, there have been no new safety concerns, according to Dr. Warren. He described this drug as “well tolerated,” adding that no significant laboratory abnormalities have been observed on long-term treatment. Although there has been a trend for increased risk of viral infections, such as herpes zoster, relative to apremilast, cases have so far been mild.

The Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR) has been approved for psoriatic arthritis, and numerous other JAK inhibitors are now in clinical trials for plaque psoriasis. These agents vary for their relative selectivity for JAK1, 2, and 3 kinases, but deucravacitinib is the first JAK inhibitor to reach clinical trials that target TYK2, which inhibits interleukin-23 and other cytokines implicated in the pathogenesis of plaque psoriasis.

“Deucravacitinib is very distinct from the other JAK inhibitors, and I think we are seeing this in the clinical studies,” Dr. Warren said. As a result of responses in the POETYK PRO trials that rival those achieved with monoclonal antibodies, he expects this drug, if approved, to be an important option for those with moderate to severe disease who prefer oral therapies.

Mark G. Lebwohl, MD, professor of dermatology and dean for clinical therapeutics, Icahn School of Medicine at Mount Sinai, New York, shares this opinion. In an interview, he emphasized the unique mechanism of deucravacitinib and its clinical potential.

“Unlike other less specific JAK inhibitors, deucravacitinib has a unique binding site on TYK2, the regulatory domain of the molecule. This makes deucravacitinib more targeted and therefore safer than other JAK inhibitors,” said Dr. Lebwohl.

“After cyclosporine, which has many side effects, deucravacitinib is the most effective oral therapy we have for psoriasis and one of the safest,” he added.

The POETYK PSO-1 and PSO-2 trials received funding from Bristol-Myers Squibb. Dr. Warren has financial relationships with AbbVie, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and Xenoport. Dr. Lebwohl has financial relationships with more than 20 pharmaceutical companies, including Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Kleinman is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Kleinman have no relevant financial disclosures.

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.

Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly, compared with placebo.

Findings were published in the New England Journal of Medicine. 

COVID-related hospitalization or death from any cause occurred in 18 of 1,355 patients (1.3%) in the group getting 2,400 mg infusions of the study drug, compared with 62 (4.6%) of 1,341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.

Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Fla., said in an interview that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes, or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.

“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
 

Researchers seek lowest doses

This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1,200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).

Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs. 14 days; P < .001 for both comparisons).

Dr. Weinreich said in an interview that trials will continue to find the lowest effective doses that can stand up to all evolving variants.

“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”

Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.

“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Dr. Weinreich said.

In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups. 

William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
 

COVID-19 a moving target

However, Dr. Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.

“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.

Dr. Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the Food and Drug Administration, with positive results.

REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain postexposure prophylaxis settings.

“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Dr. Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”  

Dr. Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.

However, he said in an interview, “how much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”

“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that – a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.

Dr. Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”

The results from this paper “are one piece of a large, multistudy, phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut – all of them – have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Dr. Weinreich said.

He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including pre-exposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”

The study is funded by Regeneron and the Department of Health & Human Services. Dr. Weinreich is a vice president of Regeneron. Dr. Joshi reported no relevant financial relationships. Dr. Fales holds stock in Eli Lilly.

A version of this article first appeared on Medscape.com.

A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.

Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly, compared with placebo.

Findings were published in the New England Journal of Medicine. 

COVID-related hospitalization or death from any cause occurred in 18 of 1,355 patients (1.3%) in the group getting 2,400 mg infusions of the study drug, compared with 62 (4.6%) of 1,341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.

Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Fla., said in an interview that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes, or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.

“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
 

Researchers seek lowest doses

This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1,200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).

Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs. 14 days; P < .001 for both comparisons).

Dr. Weinreich said in an interview that trials will continue to find the lowest effective doses that can stand up to all evolving variants.

“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”

Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.

“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Dr. Weinreich said.

In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups. 

William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
 

COVID-19 a moving target

However, Dr. Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.

“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.

Dr. Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the Food and Drug Administration, with positive results.

REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain postexposure prophylaxis settings.

“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Dr. Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”  

Dr. Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.

However, he said in an interview, “how much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”

“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that – a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.

Dr. Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”

The results from this paper “are one piece of a large, multistudy, phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut – all of them – have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Dr. Weinreich said.

He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including pre-exposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”

The study is funded by Regeneron and the Department of Health & Human Services. Dr. Weinreich is a vice president of Regeneron. Dr. Joshi reported no relevant financial relationships. Dr. Fales holds stock in Eli Lilly.

A version of this article first appeared on Medscape.com.

A monoclonal antibody combination of casirivimab and imdevimab (REGEN-COV) significantly reduced the risk of COVID-19–related hospitalizations and death from any cause in the phase 3 portion of an adaptive trial of outpatients.

Researchers, led by David Weinreich, MD, MBA, executive vice president of the drug cocktail’s manufacturer Regeneron, found in the randomized trial that the combination also resolved symptoms and reduced the SARS-CoV-2 viral load more quickly, compared with placebo.

Findings were published in the New England Journal of Medicine. 

COVID-related hospitalization or death from any cause occurred in 18 of 1,355 patients (1.3%) in the group getting 2,400 mg infusions of the study drug, compared with 62 (4.6%) of 1,341 in the matching placebo group, indicating a relative risk reduction of 71.3%; P < .001.

Sunil Joshi, MD, president of the Duval County Medical Society Foundation and an immunologist in Jacksonville, Fla., said in an interview that these findings confirm benefits of REGEN-COV and are very good news for a patient group that includes those age 65 and older with high blood pressure, diabetes, or obesity; and for people not vaccinated, who are all at high risk of hospitalization or death if they get COVID-19.

“Vaccines are critically important,” he said, “but if you were to be infected and know that there’s a way to keep yourself out of the hospital, this is very good news.”
 

Researchers seek lowest doses

This trial found that the effect was similar when researchers cut the doses in half. These outcomes occurred in 7 of 736 (1%) of patients given 1,200 mg of REGEN-COV and in 24 (3.2%) of 748 in the matching placebo group (relative risk reduction, 70.4%; P = .002).

Symptoms were resolved on average 4 days earlier with each REGEN-COV dose than with placebo (10 days vs. 14 days; P < .001 for both comparisons).

Dr. Weinreich said in an interview that trials will continue to find the lowest effective doses that can stand up to all evolving variants.

“This is one of those settings where you don’t want to underdose. You’ve got one shot at this,” he said. “We’d love to do lower doses. It would be more convenient and we could treat more patients, but if it generates more clinical failures or doesn’t work with certain variants, then you’ve done a huge disservice to the world.”

Also new in this study is that researchers tested not only seronegative patients, but patients at high risk regardless of blood antibody status, he said.

“It’s the first suggestion of data that if you’re breaking through a vaccine and you’re at high risk, the use of the cocktail is something to strongly consider because treatment early is better than treatment later,” Dr. Weinreich said.

In addition to efficacy, the phase 3 trial demonstrated the cocktail had a good safety profile. Serious adverse events occurred more often in the placebo group (4%) than in the 1,200-mg group (1.1%) and the 2,400-mg group (1.3%). Infusion reactions (grade 2 or higher) occurred in less than 0.3% of patients in all groups. 

William Fales, MD, state medical director for the Michigan Department of Health and Human Services, said the results confirm the promise of REGEN-COV for reducing hospitalizations and death in a peer-reviewed publication.
 

COVID-19 a moving target

However, Dr. Fales noted that COVID-19 is a moving target with emerging variants. The criteria for populations at high risk have also broadened since the start of the study, he said.

“A great example is pregnancy is now included as high risk, and that would have likely been a specific contraindication of patients in this clinical trial,” he said.

Dr. Fales said Michigan has been using both REGEN-COV and the Eli Lilly combination of bamlanivimab and etesevimab, which also has an emergency use authorization (EUA) from the Food and Drug Administration, with positive results.

REGEN-COV has an EUA to treat people who are at high risk of serious consequences from COVID-19, including those who are already infected (nonhospitalized) or those in certain postexposure prophylaxis settings.

“We’re seeing very low hospitalization rates and few deaths in a state that is predominately Delta,” Dr. Fales said. “So, this makes us feel that we’re doing the right thing and supports the current efforts around the country to make monoclonal antibody therapy available to high-risk patients.”  

Dr. Joshi noted that trial results have been emerging from other monoclonal antibody cocktails with different COVID-19 patient groups.

However, he said in an interview, “how much more effective they would be than this is something we’d have to look at, as 71% effectiveness in keeping people out of the hospital is pretty good for any treatment.”

“These are great numbers, but vaccination itself keeps you from getting the disease in the first place and not just for a short time period. This treatment is just that – a treatment. It gets you through that episode but it doesn’t mean you won’t get sick again. You don’t develop an immune response as you do with the vaccine,” he said.

Dr. Weinreich agreed: “This is not a substitute for a vaccine except for the small group who get the vaccine and their bodies can’t respond to it because they’re significantly immunocompromised.”

The results from this paper “are one piece of a large, multistudy, phase 3 program that basically spans from prophylaxis all the way to hospitalization and pretty much the gamut – all of them – have worked. All of these studies have shown dramatic improvement in whatever the definitive regulatory endpoint is,” Dr. Weinreich said.

He said discussions are ongoing for full regulatory approval in the United States and for expanding the EUA for other populations, including pre-exposure prophylaxis, “which the [United Kingdom’s] authority has already granted us but the FDA has not.”

The study is funded by Regeneron and the Department of Health & Human Services. Dr. Weinreich is a vice president of Regeneron. Dr. Joshi reported no relevant financial relationships. Dr. Fales holds stock in Eli Lilly.

A version of this article first appeared on Medscape.com.